While topical microbicides have a long history of use for prophylaxis against STIs in men, dating back to World Wars I and II, no subsequent clinical trials have examined the efficacy of topical microbicides used on the external genitalia of men to prevent transmission and/or acquisition of STIs, including HIV infection. We plan to (1) assess male genital hygiene, sexual practices, and attitudes about potential topical microbicide use for STI prevention in a fishing community in Kisumu, Kenya where the frequent casual and commercial sex activity of men while away from home place them at high risk for STD/HIV; (2) conduct a randomized Idouble-blinded placebo-controlled crossover Phase 1 trial of the safety, acceptability, and frequency of use Iof a topical microbicide containing 62% ethanol in emollient gel among 30 uncircumcised men over a 6-week Period; and (3) conduct a Phase 2/3 randomized double-blinded placebo-controlled trial among 1030 men to further test the safety of this microbicide and determine its efficacy in reducing the incidence of selected STIs in men using the microbicide over a follow-up period of 1-2 years (average of 21 months). For aim 1, we plan a combination of quantitative and qualitative data collection methods including focus group discussions, in-depth open-ended key informant interviews, and structured interviews to guide development of community support, recruitment and achieving adherence to intervention protocols. The Phase 1 trial will compare safety and acceptability of repeated microbicide use. The Phase 2/3 trial will further assess the safety and the efficacy of this microbicide among men to reduce the incidence of acquired infections with pathogens known or very likely to be highly ethanol-sensitive, including the enveloped viruses HSV-2 and HIV, and the bacterial pathogens which infect the epidermis of the penis, causing genital ulcer disease. The 62% ethanol-emollient gel formulation is very rapidly microbicidal, inexpensive and well-tolerated on hands, commercially available, widely used in health care settings for antisepsis on hands, and available over-the-counter for domestic use in the US. In a stepwise series of studies in Kenyan men, we have obtained preliminary data on the safety and acceptability of this product for topical use on the penis, and are currently evaluating the effects of regular use of this product by men on the vaginal flora of their female partners.